Gene signature fingerprints stratify SLE patients in groups with similar biological disease profiles: a multicentre longitudinal study
Jazyk angličtina Země Velká Británie, Anglie Médium print
Typ dokumentu multicentrická studie, časopisecké články, práce podpořená grantem
Odkazy
PubMed
35143620
PubMed Central
PMC9629374
DOI
10.1093/rheumatology/keac083
PII: 6526411
Knihovny.cz E-zdroje
- Klíčová slova
- biomarkers, childhood-onset SLE, clustering analysis, disease activity, gene signatures, interferon, neutrophils, plasma cells,
- MeSH
- dítě MeSH
- genové regulační sítě MeSH
- lidé MeSH
- longitudinální studie MeSH
- shluková analýza MeSH
- systémový lupus erythematodes * MeSH
- transkriptom * MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
OBJECTIVES: Clinical phenotyping and predicting treatment responses in SLE patients is challenging. Extensive blood transcriptional profiling has identified various gene modules that are promising for stratification of SLE patients. We aimed to translate existing transcriptomic data into simpler gene signatures suitable for daily clinical practice. METHODS: Real-time PCR of multiple genes from the IFN M1.2, IFN M5.12, neutrophil (NPh) and plasma cell (PLC) modules, followed by a principle component analysis, was used to identify indicator genes per gene signature. Gene signatures were measured in longitudinal samples from two childhood-onset SLE cohorts (n = 101 and n = 34, respectively), and associations with clinical features were assessed. Disease activity was measured using Safety of Estrogen in Lupus National Assessment (SELENA)-SLEDAI. Cluster analysis subdivided patients into three mutually exclusive fingerprint-groups termed (1) all-signatures-low, (2) only IFN high (M1.2 and/or M5.12) and (3) high NPh and/or PLC. RESULTS: All gene signatures were significantly associated with disease activity in cross-sectionally collected samples. The PLC-signature showed the highest association with disease activity. Interestingly, in longitudinally collected samples, the PLC-signature was associated with disease activity and showed a decrease over time. When patients were divided into fingerprints, the highest disease activity was observed in the high NPh and/or PLC group. The lowest disease activity was observed in the all-signatures-low group. The same distribution was reproduced in samples from an independent SLE cohort. CONCLUSIONS: The identified gene signatures were associated with disease activity and were indicated to be suitable tools for stratifying SLE patients into groups with similar activated immune pathways that may guide future treatment choices.
Department of Immunology Erasmus MC
Department of Paediatric Rheumatology Amalia Children's Hospital Radboudumc
Department of Paediatric Rheumatology St Maartenskliniek Nijmegen
Northcott M, Gearing LJ, Nim HT. et al. Glucocorticoid gene signatures in systemic lupus erythematosus and the effects of type I interferon: a cross-sectional and in-vitro study. Lancet Rheumatol 2021;3:e357–70.